The lithium ion battery has become one of the most important technologies of the 21st century due to the wide scale adoption of consumer electronics and the ambitious goals to transition away from carbon based energy sources in the coming decades. However, this rapid scaling of Li-ion battery technology has begun to put strain on the critical metals supply chain especially lithium. As most of the world’s lithium resource exists in unconventional water sources (i.e., brines, seawater, oil and gas flowback water), the direct electrochemical separation method is attractive as a selective and environmentally friendly approach. The key challenge for this technology’s success is the development of selective insertion electrodes that are well suited for the complex electrolyte environments. In this dissertation, we introduce layered transition metal oxides as a highly selective electrode material for the separation of Li+ from Na+ in solution. In Chapter 2, I will demonstrate layered cobalt oxide as a model material for the electrochemically driven separation of Li+ from Na+ in a mixed cation solution. In this environment, the layered cobalt oxide undergoes a spontaneous non-Faradaic ion exchange process to form a phase separated material containing a Li-rich and Na-rich phase. In Chapter 3, I then will discuss the importance of particle size for the reversibility of the ion exchange process so that the two-phase equilibrium can be restored after intercalation. From there, I will define a descriptor of the ion exchange characteristic time and compare it to the intercalation process characteristic time. This relationship is key for understanding and controlling the ion insertion competition between Li+ and Na+. In Chapter 4, I will continue to shrink the particle size until the surface energy effects are no longer negligible. The important role of Na+ is identified as a pillaring ion while also maintaining fast ion exchange kinetics and Li+ selectivity. In Chapter 5, I will use transmission X-ray microscopy to look at the large particles of ion exchanged layered (NaLi)xCoO2 to understand the reasons that it cannot ion exchange back to the equilibrium after intercalation. The effects of grain boundaries, particle fracturing, and phase transformation are identified as features that hinder reversible ion exchange. Finally, Chapter 6 summarizes these findings that enabled the demonstration of 9.7×104 Li+ selectivity with 99% purity Li+ recovery from an initial 1:1000 Li: Na molar ratio solution using 115 mAh/g capacity with good reversibility.