Ronaldo reached the landmark by grabbing Real Madrid's second goal against Getafe on Sunday (AEDT) after Gareth Bale had opened the scoring.
The Portugal star has reached 300 LaLiga goals in just 286 appearances, notably quicker than Lionel Messi, who needed 334 outings to bring up his triple-century.
Ronaldo had a slow start to the campaign, scoring only twice in the league before December as Madrid made a poor title defence.
However, since returning from the mid-season break, Ronaldo has been on fire, the 33-year-old scoring 11 goals in his past seven appearances.
Here are some numbers surrounding his incredible goalscoring prowess in LaLiga, thanks to Opta data.
33 - Ronaldo has hit an amazing 33 hat-tricks in LaLiga, most recently netting a treble in a 5-2 defeat of Real Sociedad at Santiago Bernabeu. He could have had 34, but unselfishly allowed out-of-form colleague Karim Benzema to take a late penalty when on a brace against Deportivo Alaves.
23 - Perhaps that moment was payback for Benzema, who has teed up 23 of Ronaldo's goals. The French striker is the most prolific assister for Ronaldo, with Mesut Ozil (20), Gareth Bale (17) and Angel Di Maria (15) not too far behind.
61 - Critics have labelled him 'Penaldo', and more than a fifth of Ronaldo's 300 goals have come from the penalty spot. He also has 20 goals in Spain's top flight from direct free-kicks.
5 - Out of Ronaldo's 33 hat-tricks in LaLiga, five of them have come in games against Sevilla. He has three trebles against a quartet of opponents: Celta Vigo, Espanyol, Atletico Madrid and Getafe.
25 - Unsurprisingly, Sevilla is therefore Ronaldo's favourite opposition in LaLiga. He has hit the net 25 times against that club.
48 - Ronaldo's most prolific campaign was in 2014-2015, the striker netting an amazing 48 times in 35 appearances for a goals-per-game ratio of 1.37. Apart from his great rival Messi, Ronaldo scored over twice as many as anyone else that term.
19 - He won his fifth Ballon d'Or in 2017, but the year was Ronaldo's least effective in LaLiga since his first campaign. He scored 19 league goals, having hit at least 30 in every calendar year since his arrival from Manchester United midway through 2009.
49 - Ronaldo's aerial prowess is well-known, with 49 headed goals demonstrating his dominance. No player in LaLiga has scored as many headers as Ronaldo since he signed from United nine years ago.