The Belgium international cancelled out Willian's opener and set up Jesse Lingard for a second-half winner as Jose Mourinho's side moved back above Liverpool to within 13 points of league leaders Manchester City.
United's 2-0 win in this fixture last season was their only victory over Chelsea across 14 matches in all competitions, and it seemed that poor record was set to continue when Willian blasted home his 12th goal of the season to cap a strong first half-hour from the visitors.
Lukaku levelled before the break with his first opportunity though, combining well with Alexis Sanchez and Anthony Martial before slotting home his first goal against a team in the top eight in 2017-18.
The game seemed destined to end in a draw until substitute Lingard headed home with 15 minutes left, lifting United two points back above Liverpool and leaving the reigning champions in fifth, two behind Tottenham.
1 - Romelu Lukaku has scored 13 goals in the Premier League this season, however this was his first against a team currently in the top eight. Overdue. pic.twitter.com/bi4Qn1IwhY— OptaJoe (@OptaJoe) February 25, 2018
Chelsea's bright start saw them come within inches of taking the lead just five minutes in, with Alvaro Morata - restored to the starting line-up in the league for the first time since January 13 - crashing a volley off the crossbar from point-blank range after being picked out by Marcos Alonso.
United had looked happy to allow the visitors the early possession and showed some more attacking intent midway through the half, with Alexis Sanchez spurning a terrific chance when he prodded the ball straight at Thibaut Courtois after taking what seemed to be an unnecessary extra touch.
It proved a costly miss, as Chelsea stunned the hosts on the break 32 minutes in. Eden Hazard took the ball into the United half and played a fine reverse pass into the path of Willian, who had time to stride into the box and drill the ball past David de Gea, who should perhaps have done better.
19 - Willian has been directly involved in 19 goals in all competitions for Chelsea this season (12 goals and seven assists); his most in a single campaign for the Blues. Handful. pic.twitter.com/UnLZuq1uJC— OptaJoe (@OptaJoe) February 25, 2018
The visitors were comfortably on top but United found an equaliser six minutes before the break as their front three suddenly came to life. Sanchez fed Martial in the penalty area and the Frenchman laid the ball into the path of Lukaku, who side-footed past Courtois.
The game settled back into a stalemate as neither team looked prepared to risk a defeat, although De Gea's unconvincing stop from Danny Drinkwater led to a timely clearance by Antonio Valencia, with Alonso ready to pounce.
Sanchez had found it tough to influence proceedings but he almost created a second for Lukaku, with Courtois reacting brilliantly to tip over the Belgian's volley.
But just as the game seemed set to end level, Lingard once more emerged as United's hero, darting in behind Andreas Christensen to head in Lukaku's cross from the right and send the Stretford End into raptures.
Key Opta stats:
- Manchester United have won two of their last three matches against Chelsea (L1) – one more than they managed in their previous 14 combined against the Blues (one).
- Chelsea have lost back to back away Premier League matches for the first time since November 2015, when they were managed by Jose Mourinho.
- The Red Devils have lost just one of their last 35 home league matches against the reigning top-flight champions (W20 D14).
- Chelsea lost a Premier League match in which they scored first for the first time since last April against Crystal Palace – they had won 22 games consecutively when scoring first before today.
- Willian has scored 12 goals in all competitions this season, equalling his best tally in a season for Chelsea (also 12 in 2016-17).
- Eden Hazard has been involved in nine goals in his last eight appearances for Chelsea in all competitions (six goals, three assists).
- Romelu Lukaku found the net against one of the sides currently occupying the top eight of the Premier League for the first time this season – he had played 10 games without scoring before this match.
- Jesse Lingard has scored 13 goals in all competitions for Manchester United this season – only Lukaku (22) has scored more.
- Chelsea have only lost four of their last 55 Premier League games played on Sunday – all four defeats have been in Manchester (two against United, two against City).