To counter-weight the loss of influential players such as Simão, Miccoli, Giorgos Karagounis and Manuel Fernandes, Benfica signed Óscar Cardozo, David Luiz, Ángel Di María, Maxi Pereira, Cristian Rodríguez and more than ten others.

Santos remained for only two games: a UEFA Champions League qualifying match against Copenhagen and the Primeira Liga opener against Leixões.

He was sacked and replaced by José Antonio Camacho, who affirmed the club's presence in top European competition and guided them to second place.

In October and November, Benfica was eliminated from the Taça da Liga and the Champions League respectively, securing a UEFA Cup berth by finishing third in the latter.

Over the next three months, Camacho's team became increasingly erratic, qualifying for the Portuguese Cup semi-finals but losing crucial points in the league race.

In early March, Camacho resigned after three consecutive league draws, citing his inability to motivate the club.

His assistant Fernando Chalana then took over, but Benfica continued to disappoint; they were eliminated in the UEFA Cup and mired in second place in mid-March.

In April, the situation deteriorated further; Benfica matched their worst league defeat in 60 years, slipped to fourth place and was knocked out of the Portuguese Cup by Sporting CP.

During Benfica's season-ending North American tour after the last game of 2006–07, Fernando Santos spoke to the media about his plans for the upcoming season.

[6] The club's first addition was winger Fábio Coentrão in March,[7] followed by defenders Marco Zoro and David Luiz in May; the latter signed a five-year contract after performing well on loan.

[11] Both added options to an offence composed solely of Nuno Gomes and Mantorras, since Fabrizio Miccoli and Derlei did not renew their loan agreements.

[14] Santos also decided not to participate in the Teresa Herrera Trophy, since the tournament was too close to Benfica's first league match.

[15] On 2 July, the club began their pre-season preparations, with medical tests in the morning followed by an afternoon training session attended by 3,000 supporters.

[16][17] From the beginning, Santos lost players who had been the backbone of the previous season's team; Giorgos Karagounis departed first[18] and Anderson pressed for a transfer, deliberately missing a pre-season match.

[27] At the Guadiana Trophy, Benfica drew with Real Betis[28] and defeated Lisbon rivals Sporting CP,[29] ending their pre-season preparations four days later with a match against Estrela da Amadora.

[30] Benfica's first competitive match hosted Copenhagen on 14 August in the third qualifying round of the UEFA Champions League.

[44] In his first game, Camacho could not lead Benfica past Vitória de Guimarães, who earned a scoreless draw at Estádio da Luz.

[47] In the last match of August, Benfica confirmed their place in the group stage of the Champions League with an away win in Parken Stadium.

Their opening game in the group stage did not go as planned; they conceded an early goal by Andrea Pirlo, who scored again with an assist by Filippo Inzaghi.

"[60] October began with the club hosting Shakhtar Donetsk in a 1–0 loss to Mircea Lucescu's team on a goal by Jádson.

"[69] On the last day of October, Benfica visited the Estádio do Bonfim for their second game against Vitória de Setúbal, and the remodelled team led at half-time.

Académica goalkeeper Ricardo made two errors, allowing Luisão and Adu to score Benfica's second and third goals,[78] and Camacho credited the late win to his players' perseverance and commitment.

Ricardo Quaresma took advantage of a 42nd-minute counterattack to dribble past David Luiz and score the winning goal for Porto.

Recent acquisition Ariza Makukula scored the only goal in the 43rd minute, a 20-meter strike which fooled goalkeeper Jaromír Blažek.

Benfica had to score two and allow none to progress; Makukula hit the post in the sixth minute, and Getafe qualified with a 77th-minute goal by Juan Ángel Albín.

At half-time, the score was 1–1, but Cardozo and Rui Costa's second-half goals gave Benfica their first domestic win in March.

The hosts were undefeated at home since October, but Benfica had an opportunity to gain ground over Vitória de Guimarães (who had lost points hours earlier).

[132] It was the fourth time in Benfica's history that they lost by three goals at home, matching their worst result in the Primeira Liga.

Lisandro López scored goals in the seventh and 80th minutes to give Porto a 2–0 win, increasing the difference between them to 24 points.

Note 2: Players with squad numbers marked ‡ joined the club during the 2007–08 season via transfer, with more details in the following section.