Abstract: During ultradeep oil and gas drilling, fluid loss reducers are highly important for water-based drilling fluids, while preparing high temperature- and salt-resistance fluid loss reducers with excellent rheology and filtration performance remains a challenge. Herein, a micro-crosslinked amphoteric hydrophobic association copolymer (i.e., DADC) was synthesized using N,N-dimethyl acrylamide, diallyl dimethyl ammonium chloride, 2-acrylamido-2-methylpropane sulfonic acid, hydrophobic monomer, and pentaerythritol triallyl ether crosslinker. Due to the synergistic effects of hydrogen bonds, electrostatic interaction, hydrophobic association, and micro-crosslinking, the DADC copolymer exhibited outstanding temperature- and salt-resistance. The rheological experiments have shown that the DADC copolymer had excellent shear dilution performance and a certain degree of salt-responsive viscosity-increasing performance. The DADC copolymer could effectively adsorb on the surface of bentonite particles through electrostatic interaction and hydrogen bonds, which bring more negative charge to the bentonite, thus improving the hydration and dispersion of bentonite particles as well as the colloidal stability of the drilling fluids. Moreover, the drilling fluids constructed based on the DADC copolymer exhibited satisfactory rheological and filtration properties (FLHTHP = 12 mL) after aging at high temperatures (up to 200 °C) and high salinity (saturated salt) environments. Therefore, this work provided new insights into designing and fabricating high-performance drilling fluid treatment agents, demonstrating good potential applications in deep and ultradeep drilling engineering.