The Premier League club have paid £2 million to sign Flores, known as Chico, and the 25-year-old has signed a three-year contract to be reunited with manager Michael Laudrup.
Later in the day, the club confirmed the loan of 24-year-old de Guzman, who completed a medical and will join with the option of making the deal permanent.
Chico spent last season on loan at Laudrup's Real Mallorca, making 33 starts in La Liga.
"I'm very happy to be here,'' Chico told the club's official website. "I know I am joining a club that has been growing over the last few years and is still ambitious to go even higher.
"Having played in La Liga (Spain) and Serie A (Italy), two great leagues, it's a dream come true to play in the Premier League, one of the best, if not the best, in the world.''
Chico, who has represented Spain at Under-21 level, started his career with Cadiz and subsequently moved to Almeria before joining Genoa in the summer of 2010.
He made 15 appearances in Serie A in the 2010-11 season.
De Guzman said of s move: "Once the opportunity came along to join Swansea and Michael Laudrup it was a done deal. I didn't have to think twice about it.
"I watched Premier League football every week on the TV last season. I was aware that Swansea are a good footballing side, but they really caught my eye when they beat Manchester City.
"They had a great season and I'm really looking forward to the challenge of playing on a new podium in the Premier League," added de Guzman, the former Dutch Under-21 international and Olympian.