The pair have gone toe-to-toe in just about everything whether it was league titles, Champions Leagues and Ballons d'Or.
That was epitomised by the fact that between 2008 and 2023, only two other players (Luka Modric and Karim Benzema) won the prestigious individual award.
But who else has been crucial to their team? Here, talkSPORT.com looks at the players with most goal involvements - that's goals and assists - since 2000 across Europe's top five leagues.
This means that contributions from other leagues and international fixtures, like Messi and Ronaldo at the MLS and Saudi Pro League respectively, do not count.
Starting us off it's an Italy legend who could not stop scoring for Udinese.
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20 - Antonio Di Natale
Games: 445
Goal involvements: 277
The Italy legend started off his career at Empoli, but moved to Udinese in 2004 where he was prolific.
He won the Serie A Golden Boot twice and was named in the team of the season on three occasions.
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19 - Miroslav Klose
Games: 446
Goal involvements: 279
Klose was one of the most prolific Bundesliga strikers in the 21st century, starting at Kaiserslauten before starring for Werder Bremen and then Bayern Munich.
He was a two-time Bundesliga winner before finishing his career at Lazio.
18 - Antoine Griezmann
Games: 505
Goal involvements: 287
Although born in France, he has spent his entire career in Spain's LaLiga, which has included two spells at Atletico Madrid sandwiched between his time at Barcelona.
His longevity has helped him gain a place on this list, with consistent goal and assist returns over his career.
17 - Mohamed Salah
Games: 355
Goal involvements: 297
After a tough start to his career at Chelsea, Salah has gone on to become one of the most lethal attackers in world football.
He joined Liverpool from Roma in 2017 and has become a Premier League champion and three-time Golden Boot winner.
16 - Thierry Henry
Games: 321
Goal involvements: 300
A true great of the game and remarkable, he still makes the list despite his professional career beginning in the mid-1990s with Monaco.
The four-time Premier League Golden Boot winner became an absolute legend at Arsenal, terrorising defences up and down the country.
15 - Pierre-Emerick Aubameyang
Games: 459
Goal involvements: 309
Aubameyang's struggles in his later career make it easy to forget just how prolific he was for much of his career.
He was a superstar for Borussia Dortmund and for Arsenal for most of his time at the club.
14 - Gonzalo Higuain
Games: 428
Goal involvements: 309
The Argentina striker was prolific in Europe for Real Madrid, Napoli and Juventus, winning six league titles across Spain and Italy.
Competing with superstar names like Ronaldo and Messi, he was only once named league top scorer. That was in the 2015/16 Serie A season.
13 - Edin Dzeko
Games: 509
Goal involvements: 313
Man City fans will be well aware of Dzeko's talents in front of goal and has been one of the best strikers around this century.
As well as two Premier League titles, he lifted the Bundesliga with Wolfsburg.
12 - Wayne Rooney
Games: 491
Goal involvements: 316
Manchester United's record goalscorer burst onto the scene as a teenager with Everton.
He was one of the most devastating forwards throughout his career, winning five Premier League titles.
11 - Edinson Cavani
Games: 479
Goal involvements: 318
An out-and-out lethal goalscorer who was prolific for Palermo, Napoli, PSG, before finishing in Europe with Man United.
As well as numerous league titles, he won the top scorer award in both Italy and France.
10 - Harry Kane
Games: 362
Goal involvements: 322
Kane may have never won a trophy in his career, but has been lethal for Tottenham and Bayern Munich.
The 31-year-old is a three-time Premier League golden boot winner, plus he won the Bundesliga equivalent in his first season at Bayern.
9 - Francesco Totti
Games: 459
Goal involvements: 327
The epitome of a one club man, spending his entire career with Roma.
He scored 250 Serie A goals over an illustrious career, that included one league title.
8 - Sergio Aguero
Games: 454
Goal involvements: 336
He became one of the greatest forwards in Premier League history after moving to Man City from Atletico Madrid.
Aguero helped them win five league titles, before a move to Barcelona that abruptly ended because of a heart problem.
7 - Luis Suarez
Games: 368
Goal involvements: 356
A truly devastating forward that embarrassed Premier League and LaLiga defenders for Liverpool and Barcelona.
His goal involvement-per-game ratio is up there with the very best in history.
6 - Thomas Muller
Games: 483
Goal involvements: 358
Another incredible one club man is Muller, who broke the record of most Bayern Munich appearances this season.
His goals and assists have helped him win an astonishing 12 Bundesliga titles.
5 - Karim Benzema
Games: 551
Goal involvements: 423
Benzema was part of a truly great Real Madrid team and his goals were key to that too.
Recognition of his talent came when he won the Ballon d'Or in 2022.
4 - Zlatan Ibrahimovic
Games: 467
Goal involvements: 426
Zlatan may be the opposite of a one-club man, but he's been no less prolific.
He has been a superstar in the Eredivisie, Serie A, LaLiga, Ligue 1, and Premier League - only the Bundesliga is missing from his record.
3 - Robert Lewandowski
Games: 466
Goal involvements: 460
For Borussia Dortmund, Bayern Munich and Barcelona, Lewandowski has been an unstoppable force in front of goal.
His near goal-per-game ratio has consistently proved him to be one of the all-time elite.
2 - Cristiano Ronaldo
Games: 626
Goal involvements: 646
There is a huge gap between the top two and the rest, showing just how far ahead Ronaldo and Messi have been.
Ronaldo has been at the top for Man United, Real Madrid, and Juventus in Europe - winning trophies and individual accolades everywhere he goes.
1 - Lionel Messi
Games: 578
Goal involvements: 743
What sets Messi apart is the assists, racking up 192 in LaLiga alone compared to Ronaldo's 44.
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All stats from transfermarkt.com
Sparta Rotterdam 
Ajax 
Roma 
Parma 
Dundee Utd 
Celtic 
Valencia 
Alaves 
PSV 
Feyenoord 
Bordeaux 
Rennes 
ST Etienne 
Marseille 
Monaco 
Everton 
Chelsea 
Leicester 
Wolverhampton 
Manchester Utd 
Bournemouth 
Real Madrid 
Sevilla 
Cremonese 
Sampdoria 
Tottenham 
Liverpool 
VFL Wolfsburg 
Borussia Dortmund 
Las Palmas 
Espanyol 
Monza 
Juventus 
Lens 
Paris Saint Germain 
Fiorentina 
Udinese 
Benfica 
Estoril 
Inter 
Como 
Manchester City 
Fulham 
Nottingham Forest 
Motherwell 
ST Mirren 
Rangers 
Carrarese 
Arsenal 
Ipswich