Abstract <p>The work studies self-association behavior of comb-like macromolecules with hydrophobic side chains depending on the distribution of the side chains grafting points, molar mass and the length of side chains. It is shown that the distribution of the side chains grafting points determines the morphology of the globules: sufficiently long macromolecules with a regular grafting points distribution form multidomain globules, while the globules of those with random distribution have elongated or necklace-like morphology. The change in the shape of the globule as the length of the macromolecule increases is reflected by the exponent in the scaling dependencies of the macromolecule sizes on its degree of polymerization. While for short chains this exponent corresponds to the generally accepted 1/3 for compact spherical particles, for long chains this exponent is close to that for elongated objects. Self-association shifts to the area of poor solvent with the decrease in side chains length. The indicator of these associative interactions is the Kraemer parameter. The conclusions of the study are based on the analysis of the experimental literature data, including the works by the authors, as well as novel, previously unpublished experiments and supported by molecular dynamics computer simulation. The experiment compares the hydrodynamic properties of random amphiphilic copolymers of <i>N</i>-methyl-<i>N</i>-vinylacetamide and <i>N</i>-methyl-<i>N</i>-vinylamine iodide (with different lengths of the hydrophobic side pendants (–C₁₂H₂₅, –C₁₀H₂₁, –C₈H₁₇, –C₆H₁₃)) and a homopolymer sodium polystyrene-4-sulfonate. Viscometric studies of copolymers of <i>N</i>-methyl-<i>N</i>-vinylacetamide and <i>N</i>-methyl-<i>N</i>-vinylamine iodide were carried out in a pure water, water-salt solvent NaCl of different quality.</p>