After her studies of literature and art history at the École Normale Supérieure in her hometown Paris, Mariame Clément lived in the U.S.A. and in Berlin, where she began a PhD on medieval Persian miniature painting.

After an internship at the Staatsoper Unter den Linden, she started working as an assistant director for various opera houses in Europe. In 2003, she won the third prize at the European Opera Directing Competition organised by Camerata Nuova and Opera Europa.

She made her directing debut in 2004 with Rossini's Il Signor Bruschino and Puccini's Gianni Schicchi in Lausanne, with sets and costumes by Julia Hansen. Their second production, Rossini's Il Viaggio a Reims in Bern, Oviedo and Tel-Aviv, was revived several years later in Antwerp under the direction of Alberto Zedda, with whom she collaborated again, also at the Flemish Opera, for Rossini's Armida in 2015.

She has worked in Athens (Le Comte Ory), Bern (La Traviata, Il Barbiere di Siviglia, La Bohème), Nancy (Rigoletto), Strasbourg (La Belle Hélène, Werther, Platée, Der Rosenkavalier, Die Zauberflöte, La Calisto), Antwerp/Ghent (Giasone, Agrippina), at the Theater an der Wien (Castor et Pollux and The Fairy Queen, both times under the direction of Christophe Rousset), in Graz (Faust, Die Zauberflöte), in Dortmund (Le Nozze di Figaro), in Nuremberg (Platée, Le Nozze di Figaro, Il Ritorno d'Ulisse in patria), in Glyndebourne (Don Pasquale, Poliuto), at the Opéra national de Paris (Hänsel und Gretel), in Essen (Le Grand Macabre, Salome), at the Royal Opera House (L'Etoile), at the Théâtre des Champs-Élysées (Il Ritorno d'Ulisse in Patria), in Santiago de Chile (Lulu), at the Semperoper Dresden (The Bartered Bride), and at the Bregenz Festival (Don Quichotte).

In 2014 she created Philippe Hurel's opera, Les Pigeons d'argile, at the Théâtre du Capitole in Toulouse. In 2016, she staged the French premiere of Wagner's second opera, Das Liebesverbot, at the Opéra national du Rhin. Her production of Barkouf in the same theatre in 2018 was the first performance since 1860 of this newly rediscovered major piece by Offenbach. The production received the prize for Best Rediscovery at the 2019 Oper! Awards. the same year at Bregenz Festival she directed Don Quichotte.

2020 started with the revival of Agrippina at Teatro de la Maestranza and the new production of Achille in Sciro at Teatro Real in Madrid. Later that year and during the corona crisis she semi-staged Lucrezia, Faust und Helene at Theater Darmstadt.

In 2021 for Glyndebourne festival she directed Il Turco in Italia.