Olivier Giroud gave Frank Lampard's side a deserved first-half lead on Wednesday, but the introduction of Roberto Firmino as a half-time substitute changed the game for the Reds.
Firmino quickly set up Sadio Mane for the equaliser and, in the first period of extra time, the Senegal star smashed home from his team-mate's pass again before Jorginho equalised from the penalty spot.
But it was the European champions who triumphed in the shoot-out, Alisson's deputy Adrian denying Abraham with his right leg to secure victory for Jurgen Klopp's side.
The Blues had been on top for large periods of an engrossing contest after Europa League final hero Kepa Arrizabalaga saved from Mohamed Salah early on, Pedro thudding a drive against the crossbar with full debutant Adrian then doing well to keep out Mateo Kovacic.
Chelsea led in the 36th minute, Christian Pulisic's ball finding Giroud's clever run beyond the back line with the France forward slotting home past Adrian.
Pulisic thought he had added a second when he cut in off the left wing to fire into the bottom-left corner, but a belated offside flag halted his celebrations, allowing Liverpool to draw level three minutes after the interval.
Substitute Firmino created the equaliser, bringing down Fabinho's lofted pass and nudging an unselfish sideways pass to Mane, who beat Kepa at the second attempt.
Chelsea were grateful to Kepa for a remarkable double save with 15 minutes of normal time to go, the goalkeeper pushing away Salah's deflected drive before then reacting sharply to turn Virgil van Dijk's rebound effort on to the woodwork.
A marginal offside flag denied Chelsea a second time, Mason Mount seeing his strike ruled out, and in extra time Firmino and Mane combined again to make it 2-1. Chelsea hit back from the spot, though, Adrian bringing down Abraham to allow Jorginho to roll home the penalty.
But, after Liverpool coolly converted all five of their kicks, Abraham was the first to miss, Klopp running on the pitch to celebrate the Reds' second European trophy of 2019.
What does it mean? Another Istanbul comeback for the Reds
Liverpool fans already had happy memories of Istanbul, the city where they completed an incredible comeback against AC Milan to win the 2005 Champions League under Rafael Benitez. This victory was not as dramatic, nor as important, but helped make up for any lingering upset over losing on penalties to Manchester City in the Community Shield.
UEFA must surely rethink this showpiece using extra time rather than going straight to penalties after 90 minutes, although female referee Stephanie Frappart performed well in making history.
Returning Kante boosts Blues
N’Golo Kante was only fit for the bench in Sunday's humbling at Manchester United but his selection from the start made a world of difference in the Blues' midfield. His energy unsettled Liverpool, the World Cup winner snaffling possession back for his side in the build up to Giroud's opening goal.
Oxlade-Chamberlain short of impact
Leaving out Firmino was a surprise call from Klopp, who rectified his error at the break by withdrawing the uninvolved Alex Oxlade-Chamberlain. The England midfielder, who missed most of last season through injury, made only 13 passes during the opening 45 minutes.
Key Opta facts
- Only Barcelona and AC Milan (five) have won the UEFA Super Cup more often than Liverpool (four).
- Chelsea have now been runners-up in three consecutive UEFA Super Cup appearances (2012, 2013 and 2019) – only Barcelona and Sevilla (four each) have been runners-up more times.
- Olivier Giroud has scored 12 goals in 16 appearances in European competition for Chelsea, compared to just seven goals in 49 domestic games for the Blues.
- Sadio Mane became the first African player to score in the UEFA Super Cup since Frederic Kanoute for Sevilla against Barcelona in 2006.
Both sides return to Premier League action after an energy-sapping encounter. Liverpool's cluster of former Saints stars head to Southampton on Saturday, with Chelsea hosting Leicester City the following day.