Jakšić was born in Srpska Crnja in  Serbia. His house has been transformed into a Memorial Museum in his honour. His early education was in Temeschwar (today Romania) and Szeged (today Republic of Hungary). Jakšić lived for a time in  Veliki Bečkerek, now Zrenjanin, where he began studying painting under Konstantin Danil. Jakšić, a son of a Serbian Orthodox priest, then went on to study fine arts in Vienna and Munich, but the revolution of 1848 interrupted his education, which he was never able to finish. In the 1848 Revolution he was wounded while fighting in Srbobran. After the revolution, deceived by the Austrians after the May Assembly, he came to live in Belgrade, Principality of Serbia, where he served as a schoolteacher and in various other capacities, although he was often unemployed. Jakšić's address was in Skadarska Street, the focus of the city's bohemian life and haunt of Belgrade's artists, writers, musicians and actors. He lived there and his former home is still used as a poetry venue for occasional 'Skadarlija nights'. A political liberal, he was persecuted by authorities. He died in despair and ravaged by illness in 1878, after he had taken part in the uprising against the Turks in Bosnia and Herzegovina.

Jakšić abhorred the rationalism and materialism of his time. What he saw and painted were human beings beset with evil, yet shining for the divine within them: He remains one of the most beloved poets of the Serbs and the symbol of their national spirit.

Jakšić is one of the most expressive representatives of Serbian Romanticism. Passionate, impetuously imaginative, emotional, rebellious and imbued with romantic nationalist sentiment, his poems about freedom, his invectives against tyranny and his verses of lyric confession resonate with romantic pathos. He saw and painted Kosovo, Battle of Montenegris, and Night Watch. Visions which will resurface in his verse little by little, here and there. Both in his poetry and paintings, the purpose of Jakšić's art was primarily moral. By showing men his vision of the possibility of true freedom of the spirit, he hoped to free them from the shackles of convention and tradition, to help them realize their potentialities by trusting their intuition. His visions were also social and political. According to Serbian literary critic Jovan Skerlić, Jakšiċ was influenced mainly by Alexander Petőfy, the great Hungarian poet of the 1848 Revolution, and Lord Byron's poetry depicting the Greek War of Independence. Jakšiċ, Skerliċ felt, was perhaps too much an artist, and would see nothing but art in anything he loved .... Here Skerliċ reveals the limitations of his disillusioned middle age (shortly before his death). Jakšiċ cannot be judged, either as an artist who meddled in mysticism, or as a mystic who employed the imagery of art. His character was entirely homogeneous; each of his pursuits was closely linked up with all his other occupations, whether he were writings lyrics, epic poems, dramatic plays, novels, publishing, making a pencil sketch of the vision that floated before his eyes, or simply painting upon canvas his magnificent portraits. It is typical of him that, besides painting and colouring his songs, he should have sung them to music. During his lifetime and after, though Jakšiċ had many admirers—they included Konstantin Danil, his former art teacher, portrait painter Katarina Ivanović, Uroš Knežević, painters Pavle Čorbanović, Jovan Popović, and Đorđe Krstić, and, among the poets and writers, Laza Kostić, Simo Matavulj, Kosta Trifković, Svetozar Miletić, Jovan Jovanović Zmaj, and Vojislav Ilić.

Jakšić is one of the leaders of Serbian romanticism and one of Serbia's greatest painters in his day. Although he wrote a number of loosely organized romantic plays, his reputation rests largely on his paintings and poetry, which ranges from sonnets, lyrics, and patriotic songs to full scale epics, or, as they are sometimes called, novels in verse. His favourite theme of nature and the national cause show a clear Byronic influence.