Ruben Neves' stoppage-time penalty made sure of a crucial three points for Wolves
In a match low on clear-cut chances, Wolves went in front after three minutes when Ruben Neves' corner bounced off the knee of Palace centre-back Joachim Andersen and in off the crossbar.
A scrappy and tetchy affair was eventually settled by Neves' stoppage-time penalty as Wolves, who were bottom of the table when Lopetegui took charge in November, moved nine points clear of the relegation zone.
"They are important points for us but they are not definitive," the Wolves boss told BBC Sport. "We have to get more points. It's an important win for us."
Albert Sambi Lokonga came closest to providing a Palace equaliser before half-time but his snap-shot from eight yards out was saved by Wolves goalkeeper Jose Sa.
Palace were on top for much of the second half but struggled to create any real opportunities of note with Eberechi Eze's dipping left-footed effort from distance, tipped over by Sa, the closest they came to scoring.
"Maybe they dominated us in the second half but I don't remember them having clear chances," Lopetegui added.
"Maybe when you score so quickly sometimes you think a lot to defend this goal and sometimes you forget to do different things. We needed to have more of the ball. Palace are a good team. It's a very difficult victory for us. We had to work hard. We're happy."
Wolves offered next to nothing going forward in the last half hour but held on before Palace goalkeeper Sam Johnstone brought down Pedro Neto as he tried to atone for his own poor touch.
Neves made no mistake from the spot and sealed a win that puts Wolves level on points with 12th-placed Palace.
This was not a game that will live long in the memory, but for Wolves it could be among their most significant of the season.
Players and management may not admit it but the three points should all-but guarantee they will be playing Premier League football again next season.
Asked directly if Wolves are now safe, Lopetegui said: "No, no, no, no. We have to achieve more points."
It has been an impressive turnaround under the former Spain boss, who took over during the World Cup break with Wolves on just 10 points from 15 games.
Tonight's triumph makes it 27 from 18 under Lopetegui and lifts them to 13th.
The game rather encapsulated Lopetegui's spell so far with Wolves sturdy, solid but far from sparkling.
No-one could doubt their fight, though, and while Lopetegui despaired of his team's inability to keep the ball late in the game and invited pressure, that is something he can work on with his team over the summer as they - surely - prepare for another year in the top flight.
After three wins and a draw in interim boss Roy Hodgson's first four games, Palace suffered defeat for the first time since mid-March.
Like Wolves, they are on 37 points, and likely safe. And, despite the loss, there was still cause for optimism.
Defensively, the closest Wolves came to opening them up was in the second minute when Diego Costa found space in the box and Johnstone turned his shot behind for the corner that led to Andersen's unfortunate own goal.
From that point until Johnstone's late error, they never looked like conceding.
"I always believed the equalising goal was there," Hodgson said. "Credit to Wolves, they defended well. The second goal was one of those cold showers you have to accept from time to time."
Going forward, they will be disappointed not to have created more but they forced Wolves back for much of the second half.
Eze and Michael Olise, alongside the tireless Jordan Ayew, provided a threat but on this occasion, the final ball was just lacking.
"Nobody could suggest the players' mindset is that we're safe," the Palace boss added. "I thought it was a very energetic, intense performance. On a normal day they would have got a result. We have five more games - I want to see exactly what we did today."
-- Courtesy of BBC Sport