Simeone's milestone match came against his favourite opponents, having now won 16 out of 18 matches against neighbours Getafe without conceding - the other two being goalless draws.
Luis Suarez put Atleti in front with his eighth goal in his first 11 league games for the club, equalling Radamel Falcao's record for the most prolific Rojiblancos start this century.
Atleti could not add to their tally but safely held on to move three points clear of Real Madrid, who have played a game more and are in action against Elche later on Wednesday.
The visitors were given a let off after 14 minutes as Thomas Lemar fired an angled shot against the frame of the goal as he attempted to catch out Ruben Yanez.
But Getafe, who ended an 11-match wait for an away league win last time out on their travels, could not hold out for much longer as Suarez glanced in Yannick Carrasco's delivery.
Suarez guided over from 15 yards soon after but a bigger chance went begging for Angel Rodriguez at the other end, the forward heading straight at Jan Oblak from close range.
Oblak was called into action again just before the hour mark to keep out Jaime Mata's header with a routine stop, while Carrasco was thwarted by Yanez down low in a second half of minimal chances.
Atletico enter 2021 in top spot
With Real Madrid also ending the year in good form, Atleti could not afford to slip up at home and give their bitter rivals a chance to pounce.
This victory - a sixth in a row at the Wanda Metropolitano in the league - ensures Simeone's men will begin 2021 at the top of LaLiga and as favourites of many to stay there.
It was vintage Atletico in many ways, scoring from one of only three shots on target in a game that saw possession near enough split down the middle.
Suarez continues impressive form
The former Barcelona striker has now been involved in eight goals in his past seven LaLiga games against Getafe - six goals and two assists - including scoring in three in a row against them in LaLiga.
Atletico terminated Diego Costa's contract on Tuesday and, on the basis of Suarez and Joao Felix's form, the pair boasting 13 goals between them in the Spanish top flight this term, it is little wonder why.
