Barcelona moved up to second place with 75 points.
Thomas Tuchel continued his stunning impact in west London to become the first coach to reach back to back Champions League finals with different clubs.
The result was a body blow for Barca, who had lost just once in their previous 22 league games and no longer have the destiny of the title in their own hands.
Chelsea looked the better side in the second half as well but could not break down Real again and then had to withstand some late pressure from the hosts, who visit Stamford Bridge in the second leg on May 5.
Atletico Madrid, Real Madrid and Barcelona are all very much in contention with only eight games each left.
Guardiola's City beat Borussia Dortmund 2-1 to reach the Champions League semifinals for the first time in six years.
Diego Simeone's side got off to an ideal start when Yannick Carrasco dribbled into an empty net in the fifth minute thanks to a lucky bounce but Betis levelled with a thumping volley from Cristian Tello in the 20th.
Zinedine Zidane's side joined Atletico Madrid on 66 points and moved top of the table, although Atletico can reclaim first place when they visit Real Betis on Sunday.
Liverpool coach Juergen Klopp blasted his players for playing into Real Madrid's hands after they were outclassed in a 3-1 defeat in Tuesday's Champions League quarter-final first leg.
Real moved above Barcelona into second place on 60 points from 28 games behind Atletico.