On December 23, 1810, Carl Peter Lepsius and Friedericke Glaser announced the birth of their son Karl Richard Lepsius. He was born in Namburg-am-Sale, Germany. He attended the University of Leipzig, the University of Gottingen and the University of Berlin, where he studied archaeology, Greek, and Sanskrit. He received his Ph.D. in 1833. He then pursued his studies of Egyptology in Paris. While he attended school in Paris, he traveled to Italy, Holland, and England with the purpose of visiting Egyptian collections. He also pursued studies that proved essential to his career. They were lithography and engraving.

Though attracted to the study of Egyptology, Lepsius actually resisted concentrating on the Egyptian language until the appearance of Champollion's Grammar, when it became possible for him to undertake a systematized approach to its study. He made a comparison of the various systems of translation then in use, in an attempt to find to his satisfaction the one that was most likely to be correct. Then, in 1836, he visited Ippolito Rosellini in Italy, who had led the Tuscan contingent attached to Champollion's expedition to Egypt. This resulted in his publication, prior to even his first visit to Egypt, of Lettre a M. le Professeur Rosellini sur l'aphbet hieroglyphique in 1837. This work expanded on Champollion's explanation of the use of alphabetical signs in hieroglyphic writing.

This culminated, in 1842, with a commission by Fredrich Wilhelm IV of Prussia, proposed by Johann Eichhorn who was then Prussia's minister of instruction and endorsed by scientists Alexander von Humboldt and Robert Wilhelm Bunsen, for Lepsius to lead an expedition to Egypt and Nubia. As with earlier expeditions, he was tasked with recording monuments and bringing back to Germany many of the treasures he might discover. Included in his team were an artist named Joseph Bonomi and an English architect named James Wild, together with surveyors, other artists, draftsmen and a plaster molder. In fact, his was the best equipped and qualified of any scholarly group to follow the French Egyptologists in the entourage of Napoleon's military campaign in Egypt forty years earlier.

Lepsius lead an expedition to Egypt and Nubia in 1842. This expedition was sponsored by Fredrick William the Fourth, who was the King of Prussia. The main goal of this expedition was to get a clear study of the monuments in the Nile River Valley, recording them with precision. The expedition collected around 15,000 artifacts that were to be displayed in Berlin. He also made maps and copied the inscriptions that appeared in various tombs and temples. Almost every tomb that is known to exist in the Valley of the Kings was investigated and certain inscriptions were copied. While investigating the tomb of Set I, they decided to use the astronomical ceilings to draw star charts which later proved to be accurate.

In May of 1843, the expedition settled in the Fayoum near the remains of the Labyrinth (the Pyramid of Amenemhat III). They remained there for several months, carrying out excavations and in the process, making the first detailed plans of that monument. From there, they traveled through Middle Egypt with stops at a number of sites such as Beni Hasan and Bersheh, as they made their way up the Nile River. Not surprisingly, they only briefly visited Thebes (modern Luxor), because at that time, the custom of explorers was to move swiftly up the Nile and then examine in more detail the monuments on the return journey downriver.

In 1846, Lepsius was married. He was later appointed to the Egyptian Museum located in Berlin, Germany. He wad Keeper of the Egyptian Collection until 1855. The outcome of the expedition that Lepsius lead in 1842 was published into twelve enormous volumes.

His work was sweeping, and particularly important because it described many sites that have deteriorated today. It is important for modern enthusiasts of Egyptian antiquities to understand just how important work by such men are even in our modern era. Many inscriptions, tombs scenes and other material that would otherwise be lost to us today were, at the hands of this gifted Egyptologist, recorded for prosperity. Time and again, modern scholars must refer back to such work for there investigations, and in fact, some of the most important finds in more recent times came about because of his work. Hence, Professor Geoffrey Martin's rediscovery of the tombs of Maya, Tutankhamun's treasurer, and the king's general, Horemheb (prior to becoming Pharaoh himself), were made possible by surveys and descriptions made by Lepsius of the New Kingdom tombs at Saqqara.

Lepsius traveled back to Egypt in 1866. It is during this expedition that Lepsius found the Table of Canopus. The Table of Canopus contained inscriptions of Greek, hieroglyphic, and demontic. This led to the translations of Egyptian hieroglyphics and served as a double check on the translation of the Rosetta Stone. After this expedition, Lepsius was made Keeper of the Royal Library located in Berlin. Lepsius died on July 10, 1884, .