Founded in 1920, Osasuna first reached Segunda División in 1932. They made it to La Liga three seasons later.
The club achieved its first ever UEFA Cup qualification in 1985–86 after finishing sixth, eventually reaching the third round in the 1990–91 edition. Finishing last in 1993–94, the side spent six years in the second level. In 2005, they reached the Copa del Rey final for the first time, losing to Real Betis after extra time.
On 27 November 2005, Osasuna played their 1,000th game in La Liga. After a stellar 2005–06 domestic campaign, they made history by finishing in fourth place – equalling the best ever finish – to enter the qualifying phase for the UEFA Champions League in the following season. This achievement was made more dramatic by the suspense that was maintained until the last day of the championship in which Osasuna and Sevilla were both vying for fourth place – both eventually ended the season with the same number of points but Osasuna finished higher due to their head-to-head record. However, they did not make it to the Champions League group phase, after being eliminated by Hamburger SV in the third qualifying round, leaving the Navarrese to compete in the UEFA Cup for the fifth time.
Osasuna were drawn in Group D of the 2006–07 UEFA Cup along with Parma, Lens, Odense and Heerenveen. The club qualified for the knock-out stage, finishing second in the group, and were drawn against Bordeaux, progressing 1–0 on aggregate, drawing 0–0 away before winning 1–0 in Pamplona through an extra time winner by Javad Nekounam.
Next up were Rangers, and Osasuna again progressed following a 1–1 draw in Glasgow and a 1–0 win at home. The club was drawn against German side Bayer Leverkusen in the quarter-finals. Regarded as severe underdogs, Osasuna not only progressed to the semi-finals but did so in style (a 3–0 away win had virtually sealed the tie, but the Rojillos also won the second leg, 1–0). In the semi-finals, the club was drawn against holders and fellow Spanish side Sevilla, eventually losing 1–2 on aggregate after a 1–0 home win.
In the following two seasons, Osasuna struggled heavily in the league. In 2008–09, they only avoided relegation in the final day; being in 18th place and entering the final matchday at home to Real Madrid, the club fell behind 0–1 but came back with two goals (the decider courtesy of , a Merengue youth graduate) to remain in the top flight.
Osasuna had varied success following those seasons, but struggled again from 2012 to 2014, being relegated to the second division after an 18th-place finish in 2013–14. In the 2014-15 season, the club managed to rank one position above the relegation zone. A managerial change resulted in substantial improvement, and Osasuna won the final match of the regular 2015–16 season 0–5 away to Oviedo, finishing sixth in the table and qualifying for promotion playoffs and. They subsequently won all the playoff games – against Gimnàstic de Tarragona in the semi-final and Girona in the final – to achieve promotion once again to La Liga. Osasuna finished 2016–17 in 19th position, resulting in relegation. They could only manage 8th in their first campaign back in the second tier.
On Monday 20 May 2019, Osasuna achieved promotion back to La Liga after Granada's victory over Albacete, mathematically ensuring a promotion place with three matches left in the season. On 31 May, they defeated Córdoba to finish as 2018–19 Segunda División champions.