Ismaila Sarr scored a penalty in the 11th minute to ensure the Hornets will be playing top-flight football again next season.
🎶 SWEEEEEET CAROLINE 🎶 pic.twitter.com/Sc1TrnJo5D— Watford Football Club (@WatfordFC) April 24, 2021
Xisco's side could still overhaul Championship leader Norwich, with a five-point gap between the teams heading into the final two games.
It comes at the end of a week in which the Canaries also exorcised the demons of relegation, leaving open the possibility that the three demoted teams will all regain promotion back to the Premier League at the first attempt for the first time in history.
Bournemouth must first negotiate the play-offs, with Jonathan Woodgate's men sitting fourth despite a 1-0 loss to fellow promotion hopeful Brentford.
The Bees' win earlier in the day meant that only three points would be good enough for Xisco's men to be promoted.
Prior to his appointment last December, automatic promotion looked unlikely for Watford after dip in form under Vladimir Ivic.
However, 17 wins in 24 league games under the Spaniard have helped amass a 10-point lead over Brentford, which has just three games left to play.
"Everyone helped me, I have a big group behind me and it was an excellent run in the to the season," Xisco said.
"I have been lucky with the players, we have a great connection, when everyone works with the same ideas and passion."
Brentford is now at least guaranteed a play-off spot alongside Bournemouth, Barnsley and Swansea City almost certain to also be in the battle for the final promotion place.
Barnsley moved nine points clear of seventh-placed Reading with a hard-fought 1-0 win over struggling Rotherham United thanks to Carlton Morris's early goal.
A week after securing its promotion, Norwich closed in on the Championship title with a 3-1 win at Queens Park Rangers to maintain its five-point lead over Watford.
Xavi Quintilla, Max Aarons and Emiliano Buendia were on target for Daniel Farke's men at Loftus Road.
At the other end of the table, all of the bottom three lost to give Wayne Rooney's Derby County a reprieve despite the Rams losing 2-1 at home to Birmingham City.
Rotherham and Sheffield Wednesday, which lost 3-1 at Middlesbrough, are still four points behind Derby, although Rotherham has two games in hand to try and overturn that gap.
Bottom-of-the table Wycombe Wanderers will likely be relegated after a 2-1 defeat at Cardiff City.
The Wanderers are six points adrift of Derby but also have a 13-goal gap to bridge on goal difference.